PROJECT SUMMARY/ABSTRACT Limited data are available on the effects of antenatal opioid exposure on the brain and neurodevelopment. Most studies are limited by methodologic flaws in study design, including small sample sizes and difficulty controlling for important environmental variables. The OBOE (Outcomes of Babies with Opioid Exposure) study, an ongoing NICHD-funded longitudinal study enrolling infants with and without antenatal opioid exposure at birth and following them to 2 years of age, attempts to improve on the limitations of previous research by collecting comprehensive exposure data including infant umbilical cords, advanced neuroimaging data to evaluate brain development, and standardized and thorough information on the home environment, maternal mental health, and parenting. The OBOE consortium, comprised of 4 highly performing centers, a data coordinating center, and a neuroimaging core, has completed our goal enrollment of 200 opioid-exposed and 100 unexposed infants. In response to RFA-HD-24-014, we now propose to complete follow-up to age two in our OBOE cohort, to fulfill our main study objectives. The Cincinnati site has contributed to the OBOE study by enrolling 149 infants (94 exposed and 55 controls), completing 233 MRIs thus far, and contributing to the publication of multiple abstracts and three manuscripts using OBOE data. For this renewal grant, we will continue progress toward our aims to: 1) determine the impact of antenatal opioid exposure on brain structure and connectivity over the first two years of life; 2) define medical, developmental, and behavioral trajectories over the first two years of life in exposed infants; and 3) determine how the home environment, maternal mental health, and parenting modify trajectories of brain connectivity and neurodevelopment over the first two years of life. Our progress so far, with enrollment completed and success in following this difficult population, shows that we have the ability to successfully complete the objectives of the OBOE study.

PROJECT NARRATIVE Children exposed to opioids antenatally can have behavioral problems, lower school achievement, and changes seen on brain MRI scans compared to unexposed children. In this multicenter study, Cincinnati is one of four centers enrolling a total of 200 exposed infants and 100 unexposed controls. We will follow this cohort to age 2 to evaluate brain structure and function, examine development and behavior, and determine the relative effects of opioid exposure versus other environmental factors on outcomes.